Metastatic Breast Cancer in Germline-PALB2 Mutations Carriers
Conditions
Brief summary
The study aims at exploring the potential benefit of a PARP-inhibitor, Niraparib, in metastatic breast cancer developing in germline-PALB2 mutations carriers. This study is designed as a multicentre one-arm two-stage phase 2 clinical trial
Interventions
DRUGNiraparib
Niraparib, once daily
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Two-stage optimal Simon design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients over 18 years * PALB2 germline heterozygous mutation carrier, wild type BRCA1&2 (breast cancer 1&2) affected with metastatic breast cancer in first metastatic treatment line or beyond * Histologically or cytologically confirmed breast cancer with evidence of metastatic disease. * Triple Negative breast cancer; Patients affected with triple negative cancers should have received anthracyclines and taxanes in neo/adjuvant therapy. * Or patients with Hormonal receptor positive (HR+)/ Human epidermal growth factor receptor 2 negative (HER2-) breast cancer, with treatment failure after a second line of therapy; Estrogen Receptor/ProgesteroneReceptor breast cancer positive patients must have received and progressed on currently recommended therapies in this indication (endocrine therapy, CDK4/6 inhibitors (adjuvant or metastatic)), or have a disease form that the treating physician believes to be inappropriate for recommended therapies in this indication. * Prior therapy with an anthracycline and a taxane in an adjuvant setting. * Prior platinum allowed as long as no breast cancer progression occurred on treatment or if given in adjuvant/neoadjuvant setting, at least 12 months elapsed from last dose to study entry. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Adequate bone marrow, kidney and liver function. * Patients without visceral crisis
Exclusion criteria
* Patients with HER2 positive disease. * Untreated and/or uncontrolled brain metastases. * Patients in visceral crisis requiring chemotherapy * Cytopenia, defined with the following thresholds: (i) Neutrophil count \< 1500/mm3; Platelet count\< 100 000/mm3; Hemoglobin \<9g/dL * Prior malignancy unless curatively treated and disease-free for \> 5 years prior to study entry. Prior adequately treated non-melanoma skin cancer, in situ cancer of the cervix, ductal carcinoma in situ (DCIS) or stage I grade 1 endometrial cancer allowed. * Known HIV (Human Immunodeficiency Virus) infection. * Pregnant or breast-feeding women. * Lack of affiliation to a social security benefit plan (as a beneficiary or assignee)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate | 4 months | Complete or partial tumour response according to RECIST 1.1 criteria accounting for objective response rate in solid tumours at 4 cycles., based on the CT-Scan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 12 months | Time from inclusion to death (all-cause) or last follow-up whichever occurs first |
| Tumoral response | 12 months | Partial Response or Complete Response or Stable Disease, as per to RECIST 1.1 criteria for tumoral response, based on CT-Scan |
| Progression-free survival | 12 months | Time from inclusion to progression or death (all-cause) or last follow-up whichever occurs first |
| Adverse event rate | 72 months | Adverse events (clinical and biological) between inclusion and 72 months |
| Quality of Life variation | 12 months | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 Questionnaire, evaluated every 3 months, from inclusion to 12 month |
| Duration of response | 12 months | Time to treatment failure, defined as time between inclusion and treatment discontinuation (any reason: death, disease progression, toxicity) or last follow-up |
Contacts
Primary ContactOdile Cohen Haguenauer, MD PhD
Outcome results
None listed